Cell & Developmental Biology
Open Access

Brief Note on Cytoskeletal Filament and Diseases

Abdel Khader^{* *}Correspondence: Abdel Khader, Department of Cell Science Research, University of Al-Salam, Al-Salam, Iraq, Email:

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Description

The cytoskeleton is a remarkable and intricate network of protein filaments that underlies the cellular architecture in eukaryotic cells. It plays a crucial role in providing mechanical support, maintaining cell shape, facilitating intracellular transport, and enabling cell motility. The cytoskeleton is composed of three main types of filaments: Microfilaments (actin filaments), intermediate filaments, and microtubules. These filaments work in harmony, orchestrating a range of cellular processes critical for cell function, growth, and division.

Microfilaments (actin filaments)

Microfilaments, also known as actin filaments, are the thinnest of the cytoskeletal filaments, with a diameter of about 7-9 nanometers. They are composed of Globular actin (G-actin) monomers that polymerize into long, flexible, double-stranded helical filaments known as F-actin. Actin filaments are dynamic structures, constantly undergoing polymerization and depolymerization, which is essential for their role in cellular processes. Actin filaments have diverse functions in the cell. They are crucial for cell motility, enabling cell crawling (amoeboid movement) and muscle contraction.

In muscle cells, actin filaments interact with myosin to facilitate muscle contraction, a fundamental process for movement in multicellular organisms. Actin filaments also play a vital role in endocytosis and exocytosis, enabling the formation of vesicles during these processes. They participate in cytokinesis, the final stage of cell division, by forming a contractile ring that pinches the cell into two daughter cells. Moreover, actin filaments support the maintenance of cell shape and provide mechanical strength to the cell cortex, the outer layer of the cell just beneath the plasma membrane. They are involved in cell-cell adhesion and cell-matrix adhesion, essential for cell communication and tissue integrity.

Intermediate filaments

Intermediate Filaments (IFs) have an intermediate diameter (8-12 nanometers) between microfilaments and microtubules. Unlike actin filaments and microtubules, which are mainly composed of globular proteins, intermediate filaments are made up of fibrous proteins, each classified into different families based on their sequence homology.

The primary function of intermediate filaments is to provide mechanical stability and resistance to mechanical stress in the cell. They form a robust, flexible network that helps cells withstand physical forces experienced in tissues such as skin, muscles, and the nervous system. Different types of intermediate filaments are found in various cell types. For instance, keratin intermediate filaments are abundant in epithelial cells, providing mechanical support and protection for the skin and its appendages. In nerve cells, neurofilaments are a type of intermediate filament involved in the maintenance of axonal structure and integrity.

Microtubules

Microtubules are the thickest of the cytoskeletal filaments, having a diameter of about 25 nanometers. They are hollow, tubular structures composed of α-tubulin and β-tubulin heterodimers that polymerize into long protofilaments. These protofilaments then bind together to form a tubular structure. Microtubules are dynamic structures that undergo dynamic instability, switching between phases of growth and shrinkage. This dynamic behavior is crucial for their various cellular functions. One of the essential roles of microtubules is in intracellular transport.

Motor proteins, such as kinesins and dyneins, "walk" along microtubules, carrying organelles, vesicles, and other cellular cargo to their specific destinations within the cell. This process is essential for maintaining the organization of organelles and for trafficking materials required for cell function. Microtubules also form the mitotic spindle during cell division. They ensure proper segregation of chromosomes by attaching to kinetochores on the chromosomes and pulling them apart during mitosis. Additionally, microtubules play a role in cell motility, particularly in the form of cilia and flagella. Cilia and flagella are slender, hair-like structures that extend from the cell surface and are involved in cell movement and the movement of fluid over the cell surface.

Dynamic Regulation

The dynamic nature of cytoskeletal filaments is a key aspect of their functionality. Polymerization and depolymerization processes are tightly regulated by a variety of proteins, including actin-binding proteins, Microtubule-Associated Proteins (MAPs), and Intermediate Filament-Associated Proteins (IFAPs). For example actin-binding proteins such as profilin, cofilin, and myosin regulate the assembly and disassembly of actin filaments. Similarly, MAPs like tau and MAP2 regulate the stability and dynamics of microtubules, while IFAPs modulate the assembly and organization of intermediate filaments.

Cytoskeletal Filaments and Disease

Given the critical roles of cytoskeletal filaments in various cellular processes, it is not surprising that defects in these filaments can lead to severe human diseases. For example-

Actin-related diseases: Mutations in actin or actin-binding proteins can cause a range of disorders, including muscular dystrophies, cardiomyopathies, and intellectual disabilities.

Intermediate filament-related diseases: Mutations in intermediate filament genes, such as keratins in the skin, are associated with various skin disorders like epidermolysis bullosa simplex. Mutations in neurofilament proteins are linked to neurodegenerative diseases.

Microtubule-related diseases: Defects in microtubule-associated proteins and motor proteins are associated with neurological disorders like Alzheimer's disease and various forms of neuropathies.

Conclusion

Cytoskeletal filaments are fundamental components of eukaryotic cells, playing a central role in cell structure, motility, division, and intracellular transport. Their dynamic nature and tight regulation make them versatile and adaptable, enabling cells to respond to their environment and carry out essential functions. Understanding the mechanisms underlying cytoskeletal filament dynamics and their roles in health and disease remains an exciting area of research that continues to yield valuable insights into the complexity of cellular life.